Radio-opaque writing instruments and methods of use

ABSTRACT

A radio-opaque composition is formulated to enable a clinician to apply custom markings to a surface, such as a patient&#39;s skin or a surgical drape on the patient. More specifically, the radio-opaque composition may be used to write on the surface. The markings may be well-defined and contrast with the surface to which they are applied. Such a composition may include a liquid radio-opaque component that includes one or more radio-opaque materials that have been dissolved in a solvent, as well as a solid radio-opaque component with particles of one or more radio-opaque materials dispersed throughout a carrier, such as the solvent of the liquid radio-opaque component. Marking apparatuses that may be used to write with the radio-opaque composition are also disclosed, as are methods for using the radio-opaque composition.

CROSS-REFERENCE TO RELATED APPLICATION

A claim for priority to the Aug. 14, 2017 filing date of U.S.Provisional Application No. 62/545,478, titled RADIO OPAQUE WRITINGINSTRUMENTS AND METHODS OF USE (“the '478 Provisional Application”), ishereby made pursuant to 35 U.S.C. § 119(e). The entire disclosure of the'478 Provisional Application is hereby incorporated herein.

TECHNICAL FIELD

This disclosure relates generally to writing instruments and, morespecifically, to radio-opaque writing instruments that include aradio-opaque writing medium that is also visible in normal light,non-toxic, biocompatible, antiseptic, and that may be sterile or capableof being sterilized. This disclosure also relates to medical proceduresthat include applying radio-opaque markings, including, but not limitedto, writing radio-opaque markings, on the exterior of a patient, or anycovering over a patient.

BACKGROUND

A variety of state-of-the-art medical procedures are conducted inconnection with imaging. Common imaging modalities include x-ray, CT(computed tomography), MRI (magnetic resonance imaging), and ultrasound.Imaging may enable a clinician, such as a surgeon, to visualize featuresinside of a patient's body without requiring the clinician to make largeincisions in the patient's body and, thus, “open the body up.” Thus,imaging may enable the clinician to conduct less invasive procedures onpatients, including so-called “minimally invasive” procedures.

In one example of a minimally invasive procedure—image-guided radiationtherapy (IGRT)—real-time imaging is used to precisely deliver radiationtherapy to tumors. IGRT uses orthogonal x-rays to visualize one or moreradio-opaque fiducial markings on the skin adjacent to the tumor orimplanted within soft tissue adjacent to the tumor. These radio-opaquemarkings act as aids for real-time tracking of the radiotherapy beamduring the treatment cycle. Radiation therapy can be delivered in asingle dose (i.e., in one single procedure) or in up to five (5) doses.A robotic system delivers highly focused radiation from a single, highlycollimated beam from hundreds of angles.

Minimally invasive procedures have also become an essential part ofmodern surgical techniques with enormous benefits to healthcareincluding: (a) increased safety to patients resulting from smallerincisions, with less trauma and far less blood loss; (b) decreasedscarring, with typical incisions requiring one or two stitches orstaples to close the surgical wound; (c) faster recovery, with patientsoften being discharged the same day and requiring one to two weeks ofrecovery compared to those with traditional surgeries typicallyrequiring six to eight weeks; and (d) decreased length of hospital stay,with patients being discharged within a twenty-three (23) hour period orscheduled for outpatient surgery, resulting in a significant costsavings.

The success of many modern minimally invasive procedures requires thatthe treatment (e.g., surgery, beam placement, etc.) be targeted to aprecise location within the patient's body. Stringent requirements havebeen placed on the accuracy of targeting of minimally invasivetreatments to prevent the inadvertent performance of a procedure at thewrong site.

Imaging is used in conjunction with a variety of minimally invasivesurgical procedures. For example, endovascular treatments, such as thetreatment of peripheral arterial disease (PAD), involves image-guidedendovascular intervention. PAD affects over 8 million Americans withsignificant associated morbidity and mortality, with about 2 millionrevascularizations, bypasses, arthrectomies, and angioplasty proceduresbeing performed annually. Given the success of such procedures,physicians now advocate an “endovascular first” strategy.

As another example, imaging is used in connection with percutaneousbiopsies, a rapidly growing common procedure in oncology. Minimallyinvasive spine surgery is performed to stabilize the vertebral bones andspinal joints and/or relieve pressures applied to the spinalnerves—often as a result of conditions such as a spinal instability,bone spurs, herniated discs, scoliosis or spinal tumors. As small,undetected movements of a patient can result in catastrophic injury tothe patient, precise treatment is extremely important. In addition tothe foregoing, the use of minimally invasive procedures continues toincrease in a variety of specialties, including, but not limited to,neurovascular, gynecological, electrophysiological, orthopedic, andcritical care procedures.

Surgical errors in which a surgeon performs the incorrect procedure,operates at the wrong site, or operates on the wrong patient are likelythe third leading cause of death in the United States of America. It isbelieved that these types of surgical errors, which may occur inoperating rooms and a variety of other settings (e.g., specialprocedures units, endoscopy units, interventional radiology suites,etc.) are currently responsible for about 400,000 deaths in the U.S.each year. Wrong site surgery is widely regarded as the most common ofthese types of surgical errors. In response, the Joint Commissionpublished a Universal Protocol for Preventing Wrong Site, WrongProcedure, and Wrong Person Surgery, which places emphasis on marking ofthe incision or insertion site, especially where there is more than onepossible location for the procedure, or when performing the procedurewould adversely affect patient outcomes and quality of life.

Marking the treatment site is vital to obtaining successful outcomes.Despite the rise in image guided procedures, traditional surgical sitemarking solutions that remain invisible under fluoroscopic imaging arestill being employed. A variety of techniques have been used in aneffort to ensure that minimally invasive treatments are properlytargeted. Slight movements by the patient (e.g., those caused as thepatient breathes, as his or her heart beats, etc.) during IGRT may beaccounted for by having the patient wear a special vest that haslight-emitting diodes (LEDs) that are detected and tracked by aceiling-mounted camera array, displayed on a computer monitor, and usedto adjust the delivery of radiation according to the patient'srespiration or other movements. Thus, the system makes continuousadjustments to deliver the radiation beam to the tumor, allowing for areduced dose of radiation in treatment margins. While the LEDs enableautomated tracking of slight movements by the patient, they may not bevisible, or useful as reference points, to a clinician as he or sherelies on imaging to conduct a procedure at a particular location.Moreover, the LEDs of such a vest cannot be positioned at specificlocations on a patient's body, and they cannot provide customizedmarkings (e.g., fiducial marks, alphanumeric characters, symbols, etc.).

To date, the markers that are available to clinicians for clearly anddistinctively marking the skin of patients (e.g., to identify patients,treatment sites, treatment procedures, etc.) are visible to the nakedeye, but do not provide any indication of site location and orreferences to other anatomic landmarks when viewed under common imagingmodalities. Moreover, the markings that may be made on a patient withcurrently available markers do not remain visible after a patient hasbeen covered with drapes or other similar items; thus, concerns of wrongsite, wrong patient, and wrong-procedure are not adequately addressed.

In an effort to address these issues, some radio-opaque markings havebeen developed. These include adhesive radio-opaque markings (i.e.,stickers, decals, etc.) with pre-defined elements, such as lines,alphanumeric characters, or arrows or other symbols, that are visibleand that may be seen under one or more common types of imaging. Whilethe pre-defined elements may be placed at desired locations on apatient's skin, they do not afford the flexibility of a free-form markthat is versatile and convenient for the clinician in marking.

While the use of radio-opaque marking materials has been suggested,those marking materials suffer from many shortcomings. Theseshortcomings are largely due to the composition of the radio-opaquemarking materials that have been proposed, which are typically thick,are difficult to apply (e.g., by requiring excessive force, because theycannot be applied in a smooth, continuous manner, etc.), and do notremain on the surfaces to which they are applied (e.g., a patient'sskin, etc.). The results are easily removable marks of poor definition,limiting the ability of such a radio-opaque material to provide thetypes of instructions that are useful in properly identifying a patient,a treatment site, and a treatment procedure.

SUMMARY

This disclosure includes compositions and apparatuses for marking apatient's skin or a covering thereon. A marking composition according tothis disclosure, which may also be referred to as an “ink,” may providea mark that is visible to an individual when viewed directly and inimages obtained from one or more common imaging modalities (e.g., x-ray,CT, ultrasound, etc.). The marking composition may be formulated toenable a clinician to mark a patient's skin clearly and accurately toprovide a well-defined and unambiguous marking that contrasts with thesurface to which it is applied and that indicates the identity of thepatient, the site (e.g., surgical location, etc.) where the patient isto be treated, and/or the procedure, or treatment approach, to be taken,including any patient-specific details of the procedure.

The marking composition may be formulated to resist bleeding whenapplied to a surface (e.g., a patient's skin, a surgical drape, etc), todry quickly, and to resist being partially or completely erased (e.g.,due to perspiration by the patient; natural oils in or on the patient'sskin; fluids, such as skin prep solutions, that are applied to thepatient's skin prior to surgery; etc.). The marking composition may beable to resist erasure for a short period of time, for example, severalhours, so that markings made by the marking composition remain visiblethroughout the duration of a particular procedure, or for longer periodsof several days in order to facilitate accurate marking visualizationfor treatments that last for a few days. Such a marking composition maybe made from (e.g., comprise, consist essentially of, or consist of)non-toxic and bio-compatible materials, with the essential components ofthe marking composition comprising its components that are visible tothe human eye and its components that are opaque to one or more imagingmodalities that are commonly used in medical procedures (e.g., itsradio-opaque components, etc.).

In various embodiments, a marking composition according to thisdisclosure may include binders, radio-opaque particulates, radio-opaquesolutions, and a suitable pigment (e.g., dye, etc., such as Gentianviolet) that together form a gel or fluid of a viscosity that readilyflows and that may be readily applied to a patient's skin and/or toprotective plastic surgical films draped over the patient's skin (e.g.,after the skin has been prepared with a standard skin prepping solution,such as chlorhexidine, iodine povacrylex combined with isopropylalcohol, or the like; etc.). More specifically, the marking compositionmay be formulated for application to a patient's skin and/or to asurgical drape in discrete lines, alphanumeric characters, and/orsymbols.

A marking composition according to this disclosure may be delivered viaa marking apparatus, such as a writing instrument (e.g., a pen, etc.).The marking apparatus may deliver the marking composition to a surfacein a substantially consistent thickness, or it may be configured todeliver the marking material to the surface in a plurality of differentthicknesses.

A marking apparatus and/or a marking composition according to thisdisclosure may be configured to eliminate the tendency of the markingcomposition to dry out and ruin the marking instrument. Morespecifically, the marking apparatus and/or the marking composition maybe configured to counteract the “gumming up” that may occur when viscousmarking compositions that are loaded with high amounts of radio-opaqueingredients interact with surgical prep solutions. In a specific, butnon-limiting embodiment, the marking apparatus may include a reservoirthat holds the marking composition, as well as a re-homogenizer, such asa steel ball (steel is only one material that may be considered for theball), which can be shaken to re-homogenize the marking composition andto avoid the settling of radio-opaque particulates in the markingcomposition as the marking apparatus is stored for extended durations oftime. The reservoir holding the marking composition may be in fluidcommunication with and separated from a second chamber, which mayinclude a nozzle or an orifice with a fixed or adjustable opening,through which the marking composition can be dispensed in a controlledwidth and thickness.

In another aspect, this disclosure includes methods for performingmedical procedures and clinical treatments in which one or moreradio-opaque markings are applied to a surface of or associated with apatient undergoing the procedure or treatment.

In one aspect, a method for identifying an entry point for a minimallyinvasive medical procedure includes applying a radio-opaque marking toan exterior surface on a patient's body, such as his or her skin. Such atechnique may be useful in a variety of minimally invasive medicalprocedures, including, without limitation, laparoscopic surgicalprocedures, interventional radiology procedures, and catheterizationprocedures.

In a specific, but non-limiting embodiment, the marking composition maybe drawn onto the exterior surface of the patient's body with a markingapparatus according to this disclosure. Alternatively, a radio-opaquedecal may be applied to the exterior surface. Such a method may includeidentifying an estimated entry point for at least one instrument to beinserted into a patient's body during the minimally invasive medicalprocedure, placing a radio-opaque marking on the estimated entry point,and radiographically imaging a general location of the patient's bodywhere the at least one instrument is to be introduced into the patient'sbody. In addition to imaging the radio-opaque marking and the estimatedentry point and radiographically identifying an actual entry point, theradiographic imaging enables a clinician, such as a doctor, aphysician's assistant, or a nurse, to determine an orientation of theactual entry point relative to the radio-opaque marking and a distancebetween the actual entry point and the radio-opaque marking. With thisinformation, the clinician may identify and, optionally, mark a locationof the actual entry point relative to the location that has been marked.Optionally, the foregoing processes may be repeated to further pinpointthe actual entry point. Once a location of the actual entry point isknown, a clinician may then make an incision at that location andintroduce the at least one instrument into the incision.

In another aspect, a radio-opaque marking may be applied to an exteriorsurface of a patient, such as the patient's skin, in a radiationtreatment procedure (e.g., a procedure for treating one or more tumorswithin the patient's body, etc.). When used in such a procedure, theradio-opaque marking may identify a location on the exterior of apatient's body to which focused radiation is to be directed.

The location on the exterior of the patient's body to which theradio-opaque marking is to be applied (i.e., the location onto whichfocused radiation is to be directed during treatment of a tumor) may beidentified by any suitable technique, including, without limitation, theuse of a CT simulator. With that location precisely identified, avisible, semi-permanent (i.e., ultimately removable) radio-opaque markmay be applied to that precise location on the exterior of the patient'sbody. Thereafter, focused radiation may be directed onto thesemi-permanent radio-opaque mark to treat a tumor corresponding to thesemi-permanent radio-opaque mark. Two or more courses of radiationtreatment may be effected using the same semi-permanent radio-opaquemark. The courses of radiation may be delivered on different days fromone another. If radiation treatments occur over a long enough period oftime, a replacement mark may be applied to the exterior of the patient'sbody before a previously applied mark is completely removed, ordisappears.

In this type of method, one or more radio-opaque markings may be used toconfirm that each tumor being considered within a patient's bodycorresponds to a radio-opaque marking on the exterior of the subject'sbody. The effectiveness of the radiation treatment at each radio-opaquemarking may also be determined by comparing a location or a tumor thatcorresponds to a particular radio-opaque marking in a newly obtainedradiographic image to a location or a tumor that corresponds to the sameradio-opaque marking in one or more previously obtained radiographicimages.

In another aspect, a radio-opaque marking on the exterior of a patient'sbody may be used to identify the patient, treatment sites, anatomiclandmarks, and/or procedure to be conducted, and to mark devices thatassist the clinician in performing the procedure using common imagingmodalities. In such a method, a radio-opaque patient identifier (e.g., aname, an identification number, etc.) may be applied (e.g., writtenonto, transferred to, etc.) to a suitable location on the patient'sskin. That location of the patient's body may then be imaged. Theradio-opaque patient identifier will appear in the image, enabling aclinician who is viewing the radio-opaque patient identifier to confirman identity of the patient, the site, and the procedure while theclinician views the radiographic image. Such a radio-opaque marker mayalso ensure that the radiographic image is placed in the proper patientfile. Identifying a patient in this manner may minimize errors, ensuringthat a patient is properly diagnosed and treated.

Other aspects, as well as features and advantages of various aspects, ofthe disclosed subject matter will become apparent to those of ordinaryskill in the art through consideration of the ensuing description, theaccompanying drawings, and the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings:

FIG. 1 is a bar graph showing the calculated mass attenuationcoefficients of various liquids, including water and variousradio-opaque liquid compositions, for radiation at a representativeintensity of 100 kVp;

FIGS. 2 and 3 are charts showing the calculated mass attenuationcoefficients of the liquids whose mass attenuation coefficients arerepresented by FIG. 1 at various energies;

FIGS. 4 and 5 provide schematic representations of embodiments ofmarking apparatuses;

FIG. 6 is a visible image of visible and radio-opaque markings made onan individual's skin with an embodiment of a marking compositionaccording to this disclosure; and

FIG. 7 is a radiographic image of the visible and radio-opaque markingsmade on the individual's skin with the embodiment of marking compositionaccording to this disclosure.

DETAILED DESCRIPTION

This disclosure is directed to a marking composition and a markingapparatus useful in making clear and unambiguous markings on a patientin preparation for medical procedures, such as minimally invasivesurgeries and other procedures. The markings may identify the patient,one or more treatment sites on the patient, the procedure(s) to beconducted at each treatment site (e.g., surgical approaches, etc.), oneor more anatomic landmarks, or the like.

A marking composition according to this disclosure may include one ormore radio-opaque components. In addition, the marking composition mayinclude a liquid carrier. Optionally (e.g., essentially,non-essentially, etc.), the marking composition may also include apigment. As another option (e.g., an essential option, a non-essentialoption, etc.), the marking composition may include one or more offollowing: thickening agents, cosmetically/dermatologically acceptablevehicles, diluents, carriers, and/or binders.

The liquid carrier of the marking composition may be aqueous or organic,and include one ingredient or a mixture of ingredients. In someembodiments, the liquid carrier may include water and isopropyl alcohol.The isopropyl alcohol may evaporate quickly and, thus, facilitate quickdrying of the marking composition once it has been applied to a surface.

The radio-opaque component(s) of the marking composition may also bereferred to as “active ingredients.” The radio-opaque component(s) maybe viewed under one or more imaging modalities (e.g., x-ray, CT,magnetic resonance (MR), ultrasound, etc.) that may be used inconjunction with a medical procedure, as well as one or more componentsthat are visible to an individual without the aid of imaging (i.e., tothe “naked eye”). In some embodiments, a radio-opaque component of themarking composition may also be visible to an individual without the aidof imaging. In various embodiments, the marking composition may includea combination of one or more liquid radio-opaque components and one ormore solid radio-opaque components. More specifically, the solidradio-opaque component(s) may be carried by (e.g., homogeneouslydispersible throughout, etc.) the liquid radio-opaque component(s) andany solvent for the liquid radio-opaque component(s). The combination ofliquid and solid radio-opaque components may impart the markingcomposition with a viscosity suitable for easy flow.

In a specific, but non-limiting, embodiment, the liquid radio-opaquecomponent of a marking composition according to this disclosure may beaqueous or organic. The liquid radio-opaque component (e.g., a solventof the liquid radio-opaque component, etc.) may comprise the carrier ofthe marking composition. A liquid radio-opaque component may include aradio-opaque material that has been dissolved in a solvent. Examples ofaqueous liquid radio-opaque components include, but are not limited to,potassium iodide solution and iodine solution. The inclusion of iodinein the marking composition may impart the marking composition withantiseptic properties. In addition, the iodide and/or iodine may impartthe marking composition with a visible color (i.e., orange-brown toviolet), making the marking composition visible even without theaddition of a pigment. Examples of organic radio-opaque substances thatmay be used as the liquid radio-opaque component or in the liquidradio-opaque component include, but are not limited to, iohexol andiopamidol.

Particles of the solid radio-opaque component may be dispersible ordispersed throughout a carrier, such as the solvent for the liquidradio-opaque component or a separate carrier of the marking composition.Particles of the solid radio-opaque component may have sizes that enablethe solid radio-opaque composition to remain in suspension throughoutthe marking compositions. In various embodiments, the particles of thesolid radio-opaque component may have sizes of about 2 microns to about100 microns. The solid radio-opaque component may include one or morepure elements, oxides of elements, and/or salts of elements that arevisible under x-ray and under CT imaging. Such an element or elementalspecies may have an atomic number sufficient to render the solidradio-opaque component radio-opaque under one or more types of imagingcommonly used in medical settings (e.g., x-ray, CT, etc.) (e.g., anatomic number of 56 or greater, etc.). Non-limiting examples of suchelements or elemental species include barium (Ba) species, bismuth (Bi)species and lanthanum (La) species. Specific examples of such inorganicsalts include, but are not limited to, barium salts (e.g., bariumsulfate (BaSO₄), which is known to be safe and non-toxic to humans),bismuth salts (e.g., bismuth oxide (Bi₂O₃)), tungsten salts (e.g.,tungsten oxide (WO₃)), other salts of elemental species that have highatomic numbers, and combinations thereof. Specific embodiments of metalsthat may be used as a solid radio-opaque component of the markingcomposition include, without limitation, tungsten, bismuth, and gold.

Each radio-opaque component of a marking composition according to thisdisclosure may be included in an amount equal to 0% of the weight of themarking composition to 100% of the weight of the marking composition.That is, the marking composition may include one radio-opaque componentthat makes up part or all of the marking composition or it may include acombination of radio-opaque components that together may make up part ofthe marking composition or an entirety of the marking composition. Themarking composition may comprise or consist of (a) radio-opaquesubstance(s) that is (are) non-toxic and biocompatible.

In a specific embodiment, a marking composition may include a carrierthat comprises water and isopropyl alcohol, a liquid radio-opaquecomponent that comprises potassium iodide and iodine, and a solidradio-opaque component that includes barium sulfate and bismuth oxide.Particles of the solid radio-opaque component may be dispersible ordispersed throughout the liquid radio-opaque component; thus, the liquidradio-opaque component may function as a carrier of the markingcomposition. Optionally, the marking composition may also include apigment, such as Gentian violet. In some embodiments, the markingcomposition may consist essentially of the carrier, the liquidradio-opaque component, and the solid radio-opaque component (i.e.,other ingredients, including the pigment, are not essential to enablethe marking composition to be used in a manner that forms a uniformmarking that can be seen in visible light as well as under one or moreimaging modalities that are used in medical settings). In otherembodiments, the pigment may be an essential component of the markingcomposition. In still other embodiments, the marking composition mayconsist of the carrier, the liquid radio-opaque component, and the solidradio-opaque component or of the carrier, the liquid radio-opaquecomponent, the solid radio-opaque component, and the pigment.

When one or more liquid radio-opaque components are combined with one ormore solid radio-opaque components, the combination may provide for aflowable (e.g., low viscosity) marking composition with a desired levelof radio-opacity. More specifically, the inclusion of one or more liquidradio-opaque components in the marking composition may minimize solidsloading (i.e., the solids content, by weight) of the markingcomposition, reducing the overall viscosity of the marking compositionwhile reducing the likelihood that the solid radio-opaque component(s)will settle and increasing the stability of the marking composition. Aformulation of the marking composition may enable it to flow through anorifice of a marking apparatus (e.g., a pen, etc., with a configurationthat enables it to dispense the marking composition in a manner thatresembles writing with a conventional writing instrument) and to bereadily and effectively applied to human tissue (e.g., skin, etc.) and,optionally, to other surfaces (e.g., the surfaces of surgical drapes,etc.). For instance, the marking composition may have the consistency ofa smoothly flowing fluid that may be applied in a continuous film. Sucha marking composition may have a viscosity in a range of about 100centipoise (cP) (e.g., the viscosity of motor oil) to about 100,000 cP(or 1,000 poise (P)) (e.g., about the viscosity of toothpaste). Variousexamples of viscosities of a marking composition according to thisdisclosure include viscosities of about 70,000 cP or less, about 50,000cP or less, about 30,000 cP or less, about 10,000 cP or less, about5,000 cP or less, about 2,500 cP or less, about 1,000 cP or less, andabout 500 cP or less.

Furthermore, a combination of various radio-opaque components with oneanother may increase the attenuation coefficient of the markingcomposition, providing for higher definition imaging contrast than iscurrently available with radio-opaque marking compositions. The use oftwo or more radio-opaque components in the marking composition maysignificantly widen the range of photon energies that are used inclinical imaging and that may be absorbed and, thus, attenuated by themarking composition. Thus, the marking composition may be useful with avariety of imaging conditions or modalities.

To illustrate the effects of using a combination of liquid and solidradio-opaque components, the mass attenuation coefficient of a specificembodiment of marking composition was compared with the mass attenuationcoefficients of other substances. In particular, mass attenuationcoefficients were determined for: (A) water (to provide a baseline; (B)water with 2% iodine, by weight; (C) water with 2% iodine, by weight,and 5% potassium iodide, by weight; (D) water with 2% iodine, by weight,5% potassium iodide, by weight, and 13% barium sulfate, by weight; and(E) water with 2% iodine, by weight, 5% potassium iodide, by weight, 13%barium sulfate, by weight, and 5% bismuth oxide, by weight. The massattenuation coefficients that were calculated cover photon energiesapplicable to typical diagnostic x-ray and CT imaging (from 1 keV to 0.1MeV), approach the lower limit of therapeutic radiation, and are takenfrom the photon interaction database at the National Institute ofStandards and Technology and based on the calculations by Seltzer, asdescribed in Radiation Research 136, 147 (1993). The chart of FIG. 1shows the mass attenuation coefficient for each composition at arepresentative intensity of 100 kVp. As further radio-opaque componentsare added, the mass attenuation coefficient increases progressively.This phenomenon is consistent across all energy levels.

By comparison, if barium sulfate is used alone to attain the equivalentlevel of attenuation achieved from formulation (D) above, which has asolids loading of 13%, a solids loading of 21.7% barium sulfate, byweight, would be required. Thus, with the inclusion of the liquidradio-opaque components (i.e., iodine solution and potassium iodidesolution), the composition may provide the same level attenuation withsignificantly less (i.e., about 40%) less solids loading. Thus, thecombination of liquid and solid radio-opaque elements may enable theformulation of marking compositions that have the same ability toattenuate radiation as existing radio-opaque materials, but withsignificantly less solids loading. With less solids loading, the markingcomposition is more stable, with a reduced propensity for solidssettling, and able to flow better.

As the charts of FIGS. 2 and 3 show, the mass attenuation coefficient ofmarking materials with combinations of radio-opaque components increaseprogressively across all energy levels applicable to typical diagnosticx-ray and CT imaging (i.e., from 1 keV to 0.1 MeV), indicating that theperformance of the marking material is consistent and predictable,unlike currently available radio-opaque markers.

In embodiments where the marking composition includes a pigment, thepigment may impart the marking composition with a specific visiblecolor. As a specific, but non-limiting example, the pigment may comprisea dye, such as gentian violet (which is often used to provide pigmentfor visible medical marking compositions).

In embodiments where the marking composition includes thickening agents,binders, and/or film-forming ingredients, one or more organic and/orinorganic polymers may be included to provide any of these functions.These ingredients may enable tailoring of the viscosity of the markingcomposition (e.g., they may impart the marking composition with gel-likecharacteristics, etc.). Such ingredients may be suitable for skin careand/or drug delivery. Examples of film-forming polymers include, but arenot limited to, silicones, acrylates, cellulose compounds, polyvinylalcohol, gelatin, xanthan gum, and polyethylene glycol. The inclusion ofone or more film-forming polymers in the marking composition may impartthe marking composition with temporary indelible characteristics (e.g.,enable a marking to remain on a surface for a particular duration oftime, prevent the marking from rubbing off of the surface, etc.).

As illustrated by FIG. 4, an embodiment of a marking apparatus 10 thatis capable of dispensing a marking composition 20 may include areservoir 30 that holds the marking composition 20 and a re-homogenizer35 (e.g., a steel ball, etc.) that is capable of homogenizing themarking composition 20 in the event that any of the ingredients of themarking composition 20 separate from the remainder of the markingcomposition 20. In some embodiments, the reservoir 30 of the markingapparatus 10 may be transparent to enable a clinician to visuallydetermine whether the marking composition 20 is homogeneous and able toflow freely. After noting that the marking composition 20 is homogeneousand able to flow freely, the clinician may use the marking apparatus 10to dispense the marking composition 20 through a dispenser tip 50 thatcommunicates with the reservoir 30 to make markings on a surface.

Alternatively, in the embodiment of marking apparatus 10′ depicted byFIG. 5, the marking composition 20 may flow from the reservoir 30′ intoa chamber 40′. The chamber may, in some embodiments, be transparent toenable a clinician to view the marking composition 20 therein. Themarking composition 20 may flow from the reservoir 30′ to the chamber40′ upon actuating the dispenser 50′ of the marking apparatus 10′ (e.g.,by rotating the dispenser 50′, etc.). Such an arrangement may ensurethat the reservoir 30′ containing the marking composition 20 is notexposed to ambient air and, thus, resists drying prior to beingdispensed by the marking apparatus 10′.

As another alternative, also depicted by FIG. 5, the chamber 40′ may bemaintained under positive pressure and the marking apparatus 10′ mayinclude a user-controlled feature 55′ (e.g., a valve, etc.) thatcontrols the flow of the marking composition 20 from the chamber 40′ tothe dispenser 50′ and, thus, the flow of the marking composition 20 outof the dispenser 50′ and onto a surface.

In some embodiments, the dispenser 50, 50′ of a marking apparatus 10,10′ may include an orifice of adjustable size. Such an orifice mayenable a user (e.g., a clinician, etc.) to select a desired line width,or thickness, of markings made as the marking composition 20 passes outof the orifice of the dispenser 50, 50′.

FIG. 6 is a visible image showing application of a marking compositionaccording to this disclosure to an individual's skin with a markingapparatus according to this disclosure. The first marking (i.e., themarking on the left) is made with a marking composition that includes apigment, while the second and third markings (i.e., the marking in thecenter and the marking at the right, respectively) are made with markingcompositions that lack pigments. The markings have been defined bymarking compositions with different solids loading of radio-opaquematerial. Each of the markings is clearly visible to the naked eye. FIG.7 is an x-ray image of the same markings, illustrating that the markingsare visible under imaging that is commonly used in medical settings.

A basic embodiment of a method for preparing for surgical procedure,includes providing a marking apparatus 10, 10′, making one or morevisible and radio-opaque markings on the patient or a covering over thepatient with the marking apparatus 10, 10′, and subjecting theappropriate site to imaging (e.g., x-ray/fluoroscopy, etc.) for thepurpose of comparing the indication to one or more internal structuresassociated with the procedure. In order to mark at or near the surgicalsite, the clinician can shake the marking apparatus 10, 10′ and observethat the marking composition 20 is able to flow freely, then dispensethe marking composition 20 from the dispenser 50, 50′ of the markingapparatus 10, 10′. A marking composition according to this disclosuremay enable the clinician to make customized, precise markings on thepatient and/or on coverings over the patient. The marking may becustomized for the patient, and may include information such as thepatient's identity, the site where the procedure is to be performed, andinformation about the procedure to be performed (e.g., to assist inplacing surgical instrument access points in the patient which are oftennecessary in minimally invasive surgical procedures, etc.).

In use, after covering the operative site with the sterile surgicalfilm, the clinician can subject the site to x-ray exposure and, byreferring to the marking(s) formed by the radio-opaque composition toensure that the proper procedure is being conducted at the proper siteon the proper patient. In situations when a clinician finds that thefirst incision marking is not optimal, the marking composition may beremoved and an appropriate mark may be made at another location.

By identifying a patient with radio-opaque marking on the patient,images may be accurately matched with the appropriate patient.

Although the foregoing disclosure sets forth many specifics, theseshould not be construed as limiting the scope of any of the claims, butmerely as providing illustrations of some embodiments and variations ofelements and/or features of the disclosed subject matter. Otherembodiments of the disclosed subject matter may be devised which do notdepart from the spirit or scope of any of the claims. Features fromdifferent embodiments may be employed in combination. Accordingly, thescope of each claim is limited only by its plain language and the legalequivalents thereto.

What is claimed:
 1. A composition for use in marking a surface inconnection with an imaging-assisted medical procedure, comprising: afirst radio-opaque component comprising a first radio-opaque materialdissolved in a solvent; and a second radio-opaque component comprising asecond radio-opaque material dispersed throughout a carrier, the firstradio-opaque material and the second radio-opaque material comprisingdifferent radio-opaque materials with different radio-opaquecharacteristics.
 2. The composition of claim 1, wherein the carrierthroughout which the second radio-opaque material is dispersed comprisesthe solvent within which the first radio-opaque material is dissolved.3. The composition of claim 1, wherein the first radio-opaque componentand the second radio-opaque component are non-toxic.
 4. The compositionof claim 1, wherein the first radio-opaque material comprises at leastone of potassium iodide and iodine.
 5. The composition of claim 4,wherein the second radio-opaque material comprises at least one of anelement, an oxide of an element, and a salt of an element, with theelement having an atomic number of at least
 56. 6. The composition ofclaim 5, wherein the second radio-opaque material comprises at least onebarium sulfate, bismuth oxide, and tungsten oxide.
 7. The composition ofclaim 4, wherein the second radio-opaque material comprises at least oneof an element, an oxide of an element, and a salt of an element, withthe element having an atomic number of at least
 56. 8. The compositionof claim 7, wherein the second radio-opaque material comprises at leastone of barium sulfate, bismuth oxide, and tungsten oxide.
 9. Thecomposition of claim 7, wherein the second radio-opaque materialcomprises at least one of tungsten, bismuth, and gold.
 10. Thecomposition of claim 1, further comprising: at least one polymer capableof: enabling the composition to form a film; tailoring a viscosity ofthe composition; and/or rendering the composition at least temporarilyindelible.
 11. The composition of claim 1, further comprising: a pigmentcapable of imparting the composition with a desired color.
 12. Thecomposition of claim 1, having a viscosity of about 100 cP to about100,000 cP.
 13. The composition of claim 1, having a viscosity of about500 cP or less.
 14. The composition of claim 1, comprising: a carriercomprising water and isopropyl alcohol; with the first radio-opaquecomponent comprising potassium iodide and iodine in solution; and withthe second radio-opaque component comprising barium sulfate and bismuthoxide.
 15. The composition of claim 14, wherein: the iodine comprisesabout 2% of the weight of the composition; the potassium iodidecomprises about 5% of the weight of the composition; the barium sulfatecomprises about 15% of the weight of the composition; and the bismuthoxide comprises about 5% of the weight of the solution.
 16. Thecomposition of claim 14, further comprising: Gentian violet.
 17. Aradio-opaque writing instrument, comprising: a container; a radio-opaquemarking composition within the container, the radio-opaque markingcomposition capable of being used to write, the radio-opaque markingcomposition consisting of non-toxic, biocompatible contents, including:a liquid radio-opaque component; and a solid radio-opaque component; adispenser capable of delivering the radio-opaque marking compositionfrom the container onto a writing surface.
 18. The radio-opaque writinginstrument of claim 17, wherein the solid radio-opaque component isdispersed throughout the liquid radio-opaque component.
 19. A method forcorrelating radiographic images to a patient, comprising: placing avisible, radio-opaque marking material that includes a liquidradio-opaque component and a solid radio-opaque component on thepatient's skin, adjacent to a location of the patient's body to beradiographically imaged; and radiographically imaging the location ofthe patient's body to obtain a radiographic image, the radio-opaquepatient identifier appearing in the radiographic image.
 20. The methodof claim 19, wherein placing the visible, radio-opaque marking materialthat includes the liquid radio-opaque component and the solidradio-opaque component on the patient's skin comprises placing a markingmaterial that includes the solid radio-opaque component dispersed in theliquid radio-opaque component on the patient's skin.